The overall objective of this research is to identify the changes in the genetic material itself or its regulation which must occur for mammalian cells to undergo preneoplastic progression in response to tumor promoters. Recent results from our laboratory indicate that promotability behaves as a dominant trait. Complementation analysis is being carried out with the aim of estimating the number of different genes (and gene products) involved in determining promotability. In addition, cloning of the relevant genetic material and anlysis of its properties in direct DNA transfection experiments can now be performed.